This proposal is designed to study the nature, specificity and significance of the cytopathic isolates present in the bowel wall of patients with chronic inflammatory bowel disease. The investigations aimed at answering these questions will involve a combined microbiologic and immunologic methodologic approach. Specifically, we will investigate the nature of the cytopathic response in cell culture produced by bowel wall filtrates to establish whether the effect is due to viral agents and/or tissue associated cytotoxins. Specificity will be established by parallel study of bowel wall filtrates prepared from non-IBD control tissues. A variety of immunologic assay systems will be used to determine the presence and nature of possible host responses to the cytopathic agents isolated in culture.